Alternative transcribed 3' isoform of long non-coding RNA Malat1 inhibits mouse retinal oxidative stress

Amr. R. Ghanam; Shengwei Ke; Shujuan Wang; Ramy Elgendy; Chenyao Xie; Siqi Wang; Ran Zhang; Min Wei; Weiguang Liu; Jun Cao; Yan Zhang; Zhi Zhang; Tian Xue; Yong Zheng; Xiaoyuan Song

iScience (Jan 2023)

Alternative transcribed 3' isoform of long non-coding RNA Malat1 inhibits mouse retinal oxidative stress

Amr. R. Ghanam,
Shengwei Ke,
Shujuan Wang,
Ramy Elgendy,
Chenyao Xie,
Siqi Wang,
Ran Zhang,
Min Wei,
Weiguang Liu,
Jun Cao,
Yan Zhang,
Zhi Zhang,
Tian Xue,
Yong Zheng,
Xiaoyuan Song

Affiliations

Amr. R. Ghanam: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Shengwei Ke: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China; Department of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China
Shujuan Wang: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
Ramy Elgendy: Department of Pharmacology, College of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
Chenyao Xie: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Siqi Wang: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Ran Zhang: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Min Wei: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Weiguang Liu: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Jun Cao: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Yan Zhang: Stroke Center & Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
Zhi Zhang: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Tian Xue: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Yong Zheng: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China; Corresponding author
Xiaoyuan Song: Hefei National Research Center for Physical Sciences at the Microscale, MOE Key Laboratory of Cellular Dynamics, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China; Corresponding author

Journal volume & issue: Vol. 26, no. 1
p. 105740

Abstract

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Summary: The function of the cancer-associated lncRNA Malat1 during aging is as-of-yet uncharacterized. Here, we show that Malat1 interacts with Nucleophosmin (NPM) in young mouse brain, and with Lamin A/C, hnRNP C, and KAP1 with age. RNA-seq and RT-qPCR reveal a persistent expression of Malat1_2 (the 3’isoform of Malat1) in Malat1Δ1 (5’-1.5 kb deletion) mouse retinas and brains at 1/4th level of the full-length Malat1, while Malat1_1 (the 5’isoform) in Malat1Δ2 (deletion of 3’-conserved 5.7 kb) at a much lower level, suggesting an internal promoter driving the 3’ isoform. The 1774 and 496 differentially expressed genes in Malat1Δ2 and Malat1Δ1 brains, respectively, suggest the 3’ isoform regulates gene expression in trans and the 5’ isoform in cis. Consistently, Malat1Δ2 mice show increased age-dependent retinal oxidative stress and corneal opacity, while Malat1Δ1 mice show no obvious phenotype. Collectively, this study reveals a physiological function of the lncRNA Malat1 3’-isoform during the aging process.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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